The present invention relates generally to a vehicle for the delivery of biologically active agents. In particular this invention includes a biological vehicle formulated from a novel combination of plant extracts that can be used for the delivery of a variety of biologically active agents. Also included in this invention are methods for using the vehicle and formulations containing the vehicle.
A vehicle is a substance, usually without biological activity, which is used as a medium for the administration of pharmacologic agents. Ideally a vehicle should be nonirritating and compatible with common medications. Criteria for vehicle selection include solubility of the active agent in the vehicle and the ability of the vehicle to penetrate physical barriers such as the stratum corneum and the lipid portion of the cell membrane. Consideration must also be given to any interactions between the vehicle and the active agent, the efficiency with which the vehicle releases the incorporated active ingredient, the molecular size and the composition of the vehicle. Traditional vehicles for subcutaneous administration include oils which tend to be irritating.
Occasionally, a vehicle will have a synergistic effect, such that the final sum total of the activity in each system is greater than the sum of the components. This is highly desirable in that less of the pharmacologic agent can be used to achieve the same effect, thereby reducing or eliminating any side effects associated with higher dosages.
Aloe is an intricate plant which contains many biologically active substances. (Cohen et al. (1992) in Wound Healing/Biochemical and Clinical Aspects, 1st ed. W B Saunders, Philadelphia). Over 300 species of Aloe are known, most of which are indigenous to Africa. Studies have shown that the biologically active substances are located in three separate sections of the aloe leafxe2x80x94a clear gel fillet located in the center of the leaf, in the leaf rind or cortex of the leaf and in a yellow fluid contained in the pericyclic cells of the vascular bundles, located between the leaf rind and the internal gel fillet, referred to as the latex. Historically, Aloe products have been used in dermatological applications for the treatment of burns, sores and other wounds. These uses have stimulated a great deal of research in identifying compounds from Aloe plants that have clinical activity, especially anti-inflammatory activity. (See, e.g., Grindlay and Reynolds (1986) J. of Ethnopharmacology 16:117-151; Hart et al. (1988) J. of Ethnopharmacology 23:61-71). As a result of these studies there have been numerous reports of Aloe compounds having diverse biological activities, including anti-tumor activity, anti-gastric ulcer, anti-diabetic, anti-tyrosinase activity, (see, e.g., Yagi et al. (1977) Z. Naturforsch 32c:731-734), and antioxidant activity (International Application Ser. No. PCT/US95/07404).
Recent research has also shown that Aloe vera, a term used to describe the extract obtained from processing the entire leaf, isolated from the Aloe vera species of Aloe can be used as a vehicle for delivering the corticosteroid, hydrocortisone, administered both topically and subcutaneously to the site of inflammation. (Davis et al. (1991) JAPMA 81:1). Davis et al. studied the topical and systemic anti-inflammatory activity of Aloe vera alone and in combination with hydrocortisone acetate. This study revealed that Aloe vera contributed in an additive way to the activity of the steroid, suggesting that Aloe vera may be useful as a biological vehicle for hydrocortisone. These studies also revealed that Aloe vera assists in the penetration of hydrocortisone through the stratum corneum. Davis has also shown that Aloe vera can be used as a biological vehicle for the delivery of the estrogenic hormones, estrogen and xcex2-estradiol and androgenic hormone, testosterone propionate. (U.S. application Ser. No. 08/662,654, filed Jun. 13, 1996, entitled, xe2x80x9cMethod of Using Aloe Vera as a Biological Vehicle,xe2x80x9d now issued as U.S. Pat. No. 5,708,038, which is incorporated herein by reference in its entirety). The significance of these findings is that if used in combination with Aloe vera, the dosage of the steroid can be reduced, while maintaining its biological activity, thereby reducing or eliminating any toxic side effects associated with higher dosages. Since Aloe vera contains many hydrophilic compounds, such as enzymes, amino acids and carbohydrates, as well as, hydrophobic compounds, such as vitamins and sterols, Davis et al. postulate that pharmacologic agents of both solubilities can be placed in Aloe vera and carried through the epidermal barrier. (Davis et al. (1991) JAPMA 81:1).
The present invention includes a novel biological vehicle that can be used for the delivery of a variety of biologically active agents. The vehicle, called Maxcell(trademark), is comprised of Aloe polysaccharide fraction Immuno-10 (see U.S. patent application Ser. No. 09/169,449, filed Oct. 9, 1998, entitled xe2x80x9cProcess for the Preparation of Immunomodulatory Polysaccharides from Aloe,xe2x80x9d which is incorporated herein by reference in its entirety), aqueous extract of Ziziphus jujuba fruits, hydrophilic solvent extract of Glycyrrhiza uralensis rhizome, organic solvent extract of Piper nigrum or Piper longum, and calcium inorganic and/or organic salts. The components of Maxcell(trademark) combine to facilitate the harmony between biologically active agents and targeted cells and organs by guiding the biological active agents to their sites of action; by preventing the clearance of the agents from blood; and by protecting cells against harsh properties of biological active agents. The biological vehicle functions as a bioadhesive polymer that selectively binds to the active ingredients thereby forming a complex; the complex thus formed then selectively binds to mannose-6-phosphate receptors on the cell membrane. This serves to promote efficient delivery of the active ingredients to the target cells.
The biological vehicle of this invention can be used to deliver a variety of biologically active agents including, but not limited to nutrients and dietary supplements, such as essential minerals like iron, chromium, selenium, zinc, copper, magnesium, manganese, calcium; vitamins such as vitamins A, E, K and D, and vitamins B1, B2, B6 and B12; essential amino acids and derivatives thereof such as arginine, lysine, leucine, phenylalanine, taurine, and N, N-dimethyl glycine; anti-oxidants such as like bioflavonoids, polyphenols, beta-carotene, curcumine, catechins, anthocyanidins; hormones such as melatonin; single plant extracts such as like Echinacea, garlic, Gingko biloba, Goldenseal, Saw palmetto, Ginseng (Panex, Siberian, and American), Cat""s claw Astragalus, St John""s Wort; and combinations of the above nutrients and dietary supplements. The components of Maxcell(trademark) not only function as a classical delivery system to target bioavailability, but also emphasize the response from the targeted living cells through renewal, enhancement and protection functions. Additionally, the components of Maxcell(trademark) also combine to produce synergistic effects. Also included in the invention is a method for preparing the vehicle, methods for using the vehicle and nutritional supplement formulations containing the vehicle.
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention as claimed.